The long term objective of our research is to understand, in molecular detail, the key steps that regulate the meiotic pathway in fission yeast. This organism is chosen for its outstanding advantages of ease of manipulation by both classical genetic techniques and also by recombinant DNA. However, all eukaryotes that engage in sexual reproduction must at some stage meiosis and the problem under investigation is therefore on of broad rather than limited general interest. Several components of the meiotic pathway in S. pombe have been described. They include meiotic activators; the Pc, Pi, Mi and Mc mating-type genes, mei3+, mei2+ and also ran1+, a gene that acts as a negative regulator of meiosis of sporulation. The ran1+ gene encodes a protein kinase that appears to be regulated by the product of the mei3+ gene. The major aims of this proposal concern the ran1+ protein kinase and its regulation during the transition from vegetative growth to meiosis. The primary specific aims are as follows: 1) Purification of the ran1+ kinase and characterization of its biochemical activity. 2) Investigation of the mechanism by which the ran1+ protein kinase is inhibited by the mei3+ product. 3) Investigation of the relationship between ran1+- encoded and cAMP-dependent protein kinase. These studies will make use of mutants in the fission yeast cAMP pathway. 4) Search for substances of the ran1+ protein kinase. 5) Since ran1+ is involved not only in meiotic control but more broadly in growth control in S. pombe, we will seek homologues of this gene in the cells of higher organisms.